Attenuation of cardioprotective effect by postconditioning in coronary stenosed rat heart and its restoration by carvedilol.
BACKGROUND
The aim of this study was to assess whether and how infarct size (IS) reduction by postconditioning is modified in the heart with coronary stenosis (CS), and how beta-blocker treatment affects it.


RESULTS
The IS was assessed by 30-min acute coronary occlusion and 24-h reperfusion in rat hearts in which CS had been induced. Modification of IS by postconditioning and the effects of daily carvedilol treatment were measured, together with reperfusion injury - salvage kinase activities. Four weeks after CS induction, any reduction of IS by postconditioning was lost, whereas it reduced IS in rats without CS. In the hearts without CS, postconditioning activated both the ERK and Akt pathway. However, in the hearts with CS, postconditioning failed to do so. In hearts with CS plus daily carvedilol treatment, postconditioning reduced IS compared with the hearts without carvedilol, although postconditioning did not activate the Akt and ERK pathways.


CONCLUSIONS
CS impaired Akt and ERK activation, resulting in a failure to reduce IS by postconditioning. Carvedilol treatment restored the IS reduction by postconditioning, possibly via other mechanism(s) of the ERK and Akt pathways.
Oikawa
Masayoshi
M
First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
Yaoita
Hiroyuki
H
Watanabe
Kenichi
K
Maruyama
Yukio
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D023921:Coronary Stenosis / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D011412:Propanolamines / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases